A Heme Export Protein Is Required for Red Blood Cell Differentiation and Iron Homeostasis Export

@article{citeulike:2370086, abstract = {Hemoproteins are critical for the function and integrity of aerobic cells. However, free heme is toxic. Therefore, cells must balance heme synthesis with its use. We previously demonstrated that the feline leukemia virus, subgroup C, receptor (FLVCR) exports cytoplasmic heme. Here, we show that FLVCR-null mice lack definitive erythropoiesis, have craniofacial and limb deformities resembling those of patients with Diamond-Blackfan anemia, and die in midgestation. Mice with FLVCR that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest, which suggests that erythroid precursors export excess heme to ensure survival. We further demonstrate that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron. Thus, the trafficking of heme, and not just elemental iron, facilitates erythropoiesis and systemic iron balance. 10.1126/science.1151133}, author = {Keel, Sioban B. and Doty, Raymond T. and Yang, Zhantao and Quigley, John G. and Chen, Jing and Knoblaugh, Sue and Kingsley, Paul D. and De Domenico, Ivana and Vaughn, Michael B. and Kaplan, Jerry and Palis, James and Abkowitz, Janis L.}, citeulike-article-id = {2370086}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1151133}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/319/5864/825}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18258918}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18258918}, citeulike-linkout-4 = {http://dx.doi.org/10.1175/0065-9401(2003)030%3C0007:MSOECO%3E2.0.CO;2}, day = {8}, doi = {10.1126/science.1151133}, journal = {Science}, keywords = {science}, month = {February}, number = {5864}, pages = {825--828}, posted-at = {2008-02-13 15:24:59}, priority = {2}, title = {A Heme Export Protein Is Required for Red Blood Cell Differentiation and Iron Homeostasis}, url = {http://dx.doi.org/10.1126/science.1151133}, volume = {319}, year = {2008} }

TY - JOUR ID - citeulike:2370086 L3 - citeulike-article-id:2370086 N2 - Hemoproteins are critical for the function and integrity of aerobic cells. However, free heme is toxic. Therefore, cells must balance heme synthesis with its use. We previously demonstrated that the feline leukemia virus, subgroup C, receptor (FLVCR) exports cytoplasmic heme. Here, we show that FLVCR-null mice lack definitive erythropoiesis, have craniofacial and limb deformities resembling those of patients with Diamond-Blackfan anemia, and die in midgestation. Mice with FLVCR that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest, which suggests that erythroid precursors export excess heme to ensure survival. We further demonstrate that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron. Thus, the trafficking of heme, and not just elemental iron, facilitates erythropoiesis and systemic iron balance. 10.1126/science.1151133 IS - 5864 JF - Science EP - 828 TI - A Heme Export Protein Is Required for Red Blood Cell Differentiation and Iron Homeostasis VL - 319 SP - 825 KW - science AU - Keel, Sioban AU - Doty, Raymond AU - Yang, Zhantao AU - Quigley, John AU - Chen, Jing AU - Knoblaugh, Sue AU - Kingsley, Paul AU - De Domenico, Ivana AU - Vaughn, Michael AU - Kaplan, Jerry AU - Palis, James AU - Abkowitz, Janis PY - 2008/02/08/ UR - http://dx.doi.org/10.1126/science.1151133 ER -